engleski

Dynamic reorganization of pericentromeric and centromeric satellite repeats in the early mouse embryo

A functional centromere is in general not defined by the underlying DNA sequence, but the epigenetic modifications and structural organization of centromeric chromatin. In the mouse, centromeres comprise centric and pericentric heterochromatin. The centric region, which is the structural and functional foundation for kinetochore formation, consists of minor satellite repeats, while pericentric region, involved in sister chromatid cohesion, is composed of several megabases of major satellite repeats. In interphase nuclei, the pericentric heterochromatin coalesces to chromocenters, with the minor satellites from different chromosomes remaining separate entities. We are instrested in understanding how this particular organization is established during ebryonic development. Upon fertilization two gametes with distinct chromatin organization are united in a single cytoplasm, initialy as two separate pronuclei, which undergo asymmetric epigenetic modifications and chromatin reorganization. Using DNA FISH for major and minor satellites, we followed dynamic reorganization of the centromeric repeats during the first cell cycle up to the 2-cell stage. The somatic-like pattern in the female and the highly ordered packaging in the male gamete are quickly rearranged and assimilated to occupy restricted spatial domains sourrounding the nucleolar precursor body. A transition from this zygotic to a chromocenter-like organization of the centromere takes place during the 2-cell stage. Combining DNA FISH with immunostaning for a selection of histone modifications revealed that major satellites in male and female pronuclei are associated with distinct chromatin environments. These findings highlight the importance of ensuring a proper centromere function while preserving distinction of parental genome origin duriing the return to totipotency in the zygote.

centromeres; epigenetic modification; mouse; satellite repeats; pericentromeric heterochromatin

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